Human interleukin-4 (IL-4) is a natural protein which is believed to have a therapeutic potential against infection, cancer and autoimmune disease and was characterized by Yokota et al., Proc. Natl. Acad. Sci.,USA, 83, 5894-5898 (1986). Mouse IL-4 is reported by Lee, et al., Proc. Natl. Acad. Sci. USA, 83, 2061-2065 (1986) and Noma, et al. Nature, 319, 640-646 (1986).
In the production of genetically engineered IL-4, separation of the expressed protein from the transformed host cells or their cultures supernatants can be a major problem, Dwyer, Biotechnology, 2, 957 (1984).
E. coli expression of IL-4 in E. coli can be intracellular insoluble aggregates (inclusion bodies) or active soluble material secreted into the periplasmic space or culture medium (fermentation broth). This invention relates to extracting and purifying active soluble IL-4 resulting from its expression in certain strains of E. coli.
Clinical use of active IL-4 requires a high purity material that is not contaminated by cell constituents or cell debris of the IL-4 expressing cell. Accordingly, purification of active IL-4 in the fermentation broth of IL-4 expressing E. coli in high yields and high purity is needed.